Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With Attention-Deficit/Hyperactivity Disorder

Supernus Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Attention Deficit Hyperactivity Disorder (ADHD); Impulsive Aggression

Treatments: Drug: SPN-810; Behavioral: Point Subtraction Aggression Paradigm (PSAP) Task; Drug: Placebo; Diagnostic Test: Magnetic Resonance Spectroscopy (MRS); Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03638466

810P204

Details and patient eligibility

About

The purpose of this study is to evaluate the effect of 4-week SPN-810 treatment on brain functioning in patients aged 8-12 years with ADHD and associated feature of impulsive aggression (IA). This will be achieved using functional magnetic resonance imaging (fMRI) in conjunction with the point subtraction aggression paradigm (PSAP) Task, a behavioral aggression paradigm in which subjects are provoked by having money indirectly taken from them by a fictitious opponent, simulating an aggression response.

Full description

Approximately 30 subjects aged 8-12 diagnosed with ADHD and associated feature of IA will be recruited in this study. The PSAP is a behavioral aggression test used to evaluate behavioral response related to impulsive aggression. The task will be combined with functional MRI to evaluate the change in brain activity measured as BOLD signal (blood oxygenation level-dependent) from baseline to the end of the treatment with SPN-810.

The level of neurotransmitters Glutamate and GABA will also be measured using magnetic resonance spectroscopy (MRS).

Additionally, the improvement and severity in impulsive aggression behaviors will be assessed using validated scales.

Enrollment: 14 patients

Sex: All

Ages: 8 to 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Otherwise healthy male or female subjects, aged 8-12 years, inclusive, at the time of screening with primary diagnosis of ADHD and currently receiving monotherapy treatment with an optimized US Food and Drug Administration (FDA)-approved ADHD medication.
• Impulsive aggression (IA) will be confirmed at screening using the R-MOAS and the Vitiello Aggression Scale.

Exclusion criteria

• Current or lifetime diagnosis of epilepsy, major depressive disorder, bipolar disorder, schizophrenia or related disorder, personality disorder, Tourette's disorder, fetal alcohol syndrome, or psychosis not otherwise specified.
• Currently meeting DSM criteria for autism spectrum disorder, pervasive developmental disorder, obsessive-compulsive disorder, post-traumatic stress disorder.
• Known or suspected IQ <70, pregnancy, substance or alcohol abuse.
• Known history of implanted brain stimulator, vagal nerve stimulator, ventriculoperitoneal shunt, cardiac pacemaker, orthodontic braces, or implanted medication port. Visual and hearing (≥25 dB) impairment.
• Pre-existing medical or psychological conditions that preclude being in the MRI scanner (e.g., claustrophobia, morbid obesity, or marked anxiety about the procedure).

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

14 participants in 2 patient groups, including a placebo group

Single dose of SPN-810

Active Comparator group

Description:

Subjects will be treated with medium dose of SPN-810

Treatment:

Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI)

Diagnostic Test: Magnetic Resonance Spectroscopy (MRS)

Behavioral: Point Subtraction Aggression Paradigm (PSAP) Task

Drug: SPN-810

Placebo

Placebo Comparator group

Description:

Subjects will be treated with a matching Placebo

Treatment:

Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI)

Diagnostic Test: Magnetic Resonance Spectroscopy (MRS)

Drug: Placebo

Behavioral: Point Subtraction Aggression Paradigm (PSAP) Task